Pharmacological insights into advanced glycation end-product-associated vascular dysfunction and pulp calcification...

To investigate the involvement of advanced glycation end-products (AGEs) in intrapulpal calcification and evaluate the effects of AGE synthesis inhibition and degradation on pathological pulp changes in type 2 diabetic rats.

Five- to 11-week-old Sprague-Dawley rats and Spontaneously Diabetic Torii rats (a model of type 2 diabetes) were divided into a control group without treatment and treatment groups receiving AGE breaker or a receptor of AGE (RAGE)-antagonist for 4 weeks. Alagebrium chloride (a cross-link breaker) was administered orally at 10 mg/kg/day, and FPS-ZM1 (a RAGE inhibitor) was administered intraperitoneally at 1 mg/kg/day. The mandibles and mesenteries were evaluated post-treatment. Morphological changes were analysed using micro-computed tomography (micro-CT) and scanning electron microscopy (SEM). Histological and immunohistochemical analyses (anti-AGE, RAGE, interleukin-6, and vascular endothelial growth factor) were performed using haematoxylin and eosin and diaminobenzidine staining to assess AGE formation and vascular alterations. Data were analysed using analysis of variance, t-tests, and generalized estimating equation logistic regression.

Alagebrium significantly reduced intrapulpal calcification, whereas FPS-ZM1 did not meet the prespecified significance threshold. SEM and histology revealed suppressed AGE accumulation in the perivascular regions of the pulp in the alagebrium treatment group compared with in the untreated diabetic controls. Morphological changes were observed in the vasculature, suggesting improved tissue integrity post-treatment.

Pharmacological modulation of AGE-related pathways was associated with reduced intrapulpal calcification and pathological pulp changes in type 2 diabetic rats. These findings suggest that AGE-related processes potentially contribute to diabetic pulp pathology and warrant further investigation as likely therapeutic targets.